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First draft of Neanderthal genome is unveiled

By Ewen Callaway

The first draft of the genome of a 38,000 year-old Neanderthal is complete, scientists announced today.

Early glimpses of the genome, which was sequenced by Svante Pääbo, of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, and colleagues, have already cast new light on the ancient human species that went extinct more than 25,000 years ago.

Now study of the more complete genome will allow scientists to examine Neanderthals’ relationship with modern humans as never before.

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A preliminary analysis of the sequence suggests that Neanderthals contributed few, if any, genes to humans via inbreeding. “There’s no positive evidence that it occurred at all,” Pääbo says.

‘Terrific’ news

Chris Stringer, a palaeontologist at the Natural History Museum in London, UK, remembers hearing Pääbo announce, in the late 1990s, that his team had sequenced a few hundred letters of Neanderthal DNA.

“You couldn’t have imagined 10 years later we’d be talking about the whole genome,” Stringer says.

“I think it’s just terrific. It’s a bit like suddenly getting a Hubble telescope,” says Edward Rubin, a genomicist at the Joint Genome Institute in Walnut Creek, California. “We can study Neanderthals from a whole new vantage point.”

However, Rubin notes that the sequence is a rough draft that will need much filling in. “To feel really confident in conclusions you make from this data, it will come from going deeper or looking at other Neanderthals,” he says.

In the announcement, Pääbo said 3 billion letters of DNA comprising 60% of a male Neanderthal’s genome, as well as several million more letters from three other individuals, have now been sequenced.

Cave dweller

Pääbo’s team will continue to sequence and analyse Neanderthal DNA from all four of their samples to gain a more complete picture of the genomes, as well as genetic diversity among the species. They plan to publish their initial results later this year.

Palaeontologists discovered the bones that contributed the lion’s share of the genome in Croatia’s Vindija cave. Initial analysis of this sample and of other Neanderthal bones focused on small stretches of DNA from mitochondria, maternally inherited organelles that provide cells with energy. Mitochondrial DNA has been used extensively to study human evolution.

Yet to sequence the nuclear genome – about 180,000 times longer than a mitochondrion’s – the researchers relied on a new technology that rapidly decodes very short stretches of DNA by reading light pulses generated from forging new copies of the DNA strands.

Since more than 96% of the DNA recovered from the Vindija bone belonged to invading microbes, Pääbo’s team sequenced tens of billions of letters of DNA to get the 3 billion that they say undoubtedly belonged to Neanderthals.

Crossbreeding clues

Previous mitochondrial analysis of Neanderthal DNA has uncovered no sign that Neanderthals and humans interbred sufficiently to leave a trace. A preliminary analysis across the new genome seems to confirm this conclusion, but more sequence data could overturn this conclusion.

“I look at the fossil evidence and don’t see much evidence of intermixture,” adds Stringer.

Early glimpses at the Neanderthal genome have already trickled out in recent publications and conference presentations.

A Neanderthal recovered in Spain, seemed to have the human version of gene linked to language development, Foxp2, leading some researchers to speculate that Neanderthals communicated much like humans.

The same individual probably had a gene mutation for type O blood and at least one copy of a mutation that, in modern humans, would produce fair skin and red hair – possibly an adaptation to a cold climate with little sunshine.

Two gene mutations cast further doubt on widespread sexual relations with humans. The Vindija Neanderthal lacks a version of a brain development gene, microcephalin-1, that some researchers had hypothesised humans picked up from Neanderthals. The same goes for a mutation in a gene linked to brain ageing and Alzheimer’s called Tau.

Though evidence for or against human-Neanderthal fraternisation may draw all the popular attention, evolutionary biologists are eager to apply the data to less prurient projects. First among those will be understanding what makes humans human.

Our species has accrued millions of genetic changes since they last shared an ancestor with chimpanzees about 6 million years ago. Scientists have studied these differences to get a handle on what genetic changes contributed to human evolution.

Clean environment

With a Neanderthal genome sequence, scientists can attach even greater precision to when these mutations occurred. Most of the differences between humans and chimps undoubtedly built up before we split from Neanderthals.

But at some spots on the genome, Neanderthal and humans will differ, says James Noonan, a genomicist at Yale University in New Haven, who plans to focus on non-coding genetic changes that determine how much of a protein gets made.

Looming over the Neanderthal genome project has been the possibility of contamination from human handlers. Pääbo’s team members perform much of their work while donning containment suits in clean rooms, and they have developed sequencing techniques to ferret out contamination.

Despite these precautions, an earlier release by the same team of one million Neanderthal DNA letters in 2006 showed signs of human contamination.

Those problems appear to be solved, says Rubin, citing the 2008 publication of a complete mitochondrial genome. “From that I’m expecting that this data’s going to be largely Neanderthal.”

As to whether the sequence means we could ever resurrect our extinct cousins, Pääbo rules it out. “We will not be able to recreate the Neanderthal even if we wanted to, it would be technically impossible,” he says.